This study was led by Kevin Counterman, a medical student who had a brother affected with Duchenne, as well as additional medical students from the University of New England College of Osteopathic Medicine, in collaboration with Yaacov Anziska, MD at SUNY Downstate in Brooklyn and The Duchenne Registry team. Counterman and team analyzed Registry data collected between 2007-2019 to study possible associations between self-reported behavior and learning issues with DMD gene mutations and isoforms. Isoforms are often shorter versions of the DMD gene that are expressed in different tissues of the body, versus the main full length dystrophin that is expressed in muscle tissue. Counterman and team found that DMD mutations disrupting expression of the Dp140 and Dp71 isoforms were associated with a higher likelihood of reported behavioral and learning concerns. In other words, they found an increasing prevalence of learning and behavioral concerns the further a patient’s mutation is towards the end of the DMD gene. These associations have been reported in prior studies but all these studies have been performed using much smaller sample sizes or single centers. Utilizing data from The Duchenne Registry provided a much larger and diverse cohort and greater statistical power than previous studies.

An international team of researchers, led by Drs. Megan Waldrop and Kevin Flanigan at Nationwide Children’s Hospital, wanted to study the clinical features (phenotype) of individuals with DMD gene deletions that are the same as the deletions produced by Sarepta Therapeutics’ exon 51 skipping therapy, Exondys 51 (eteplirsen). The research team conducted a detailed review of the published literature and unpublished databases (registries) to compile the phenotypic features of patients with exon 51 “skip-equivalent” deletions, and The Duchenne Registry provided the largest number of patients. Sufficient clinical information was found on 135 patients. The majority had mild phenotypes: Becker (n = 81) or isolated dilated cardiomyopathy (n = 3). Particularly interesting are the asymptomatic (n = 10) or isolated hyperCKemia (n = 20) patients with deletions of exons 45–51, 48–51, 49–51 and 50–51. Finally, 16 (12%) had more severe phenotypes described as intermediate (n = 2) or Duchenne (n = 14), and 6 reports had no definitive phenotype. This review shows that the majority of exon 51 “skip-equivalent” deletions result in milder Becker phenotypes and supports that exon 51 skipping therapy could provide clinical benefit, although the authors acknowledge that other factors, such as age at treatment initiation or ongoing standard of care, may influence the degree of benefit.

The Duchenne Registry team wanted to investigate whether a patient’s genotype (their genetic mutation) and their sociodemographic factors (such as their race/ethnicity, where they live and their type of insurance) could be influencing their age of diagnosis of Duchenne. The team performed an analysis of both genotypic and sociodemographic factors in males with Duchenne living in the US who enrolled in the Registry from 2007 to 2019. The analysis revealed that specific genetic mutation subtypes were associated with later ages of symptom onset and diagnosis, and that as year of birth increased the age at diagnosis decreased. However, after adjusting for genotype and year of birth, the average age of diagnosis was significantly later for traditionally at-risk patients. Non-Caucasian patients and patients from high-poverty neighborhoods were older at diagnosis, and non-Caucasian patients had significantly longer periods from symptom onset to diagnosis than Caucasian patients. Medicaid/uninsured patients were diagnosed significantly later than those with private/commercial insurance. One method that could reduce the observed disparities includes increasing education of the signs and symptoms of Duchenne to primary care providers, especially those practicing in underserved areas or among at-risk populations. Another method to eliminate these disparities would be through the implementation of a national public health system such as newborn screening. The strength of this study lies in the large, geographically and socially diverse sample size made possible by the Registry, which allows for sufficient statistical power to identify factors influencing the age of diagnosis in Duchenne.

Read the PPMD blog on this article. The Catabasis team, led by Joanne Donovan, MD, PhD, wanted to gain a better understanding of corticosteroid use in the United States since the establishment of the Duchenne Care Guidelines. The researchers performed a retrospective analysis of corticosteroid use in ambulatory and nonambulatory males with Duchenne or Becker muscular dystrophy who enrolled in The Duchenne Registry from 2007 to 2016. Only data from registrants living in the US were used in this study. The analysis revealed that a considerable proportion of US participants were either not on corticosteroids or not on recommended doses despite consensus recommendations. Side effects were a consideration in initiating and discontinuing treatment. These data reinforce the need for additional treatment options for those affected by Duchenne. In addition, this work highlights the value of patient and family participation in The Duchenne Registry in order to further clinical development of new treatments for Duchenne.

Read the PPMD blog on this article. Richard Wang, PhD, Stan Nelson, MD and their team of researchers at UCLA analyzed data entirely from The Duchenne Registry. They found a correlation between certain deletions and the age at loss of ambulation. In particular, they found that boys with exon 45 deletions and boys with exon 3-7 deletions had a later age at loss of ambulation (they walked longer) than other boys in the Registry. Cultured muscle cells from Duchenne boys with deletions of exons 3–7 or exon 45 showed higher naturally occurring skipping than other mutations, providing a potential biological rationale for the prolonged ambulation. These results highlight the utility of aggregating patient-reported data to reveal progression differences, identify potentially confounding factors and probe molecular mechanisms that may affect disease severity.

Dr. Richard Finkel, a neurologist at Nemours Children’s Hospital in Orlando, and his team wanted to determine if the age at onset of ambulation (age at first steps) was significantly later for toddlers with Duchenne compared to toddlers without Duchenne. We created a survey with questions focused on this topic and almost 500 registrants completed this survey. Dr. Finkel and his team analyzed the data from the DuchenneConnect survey, as well as data from MD STARnet and the Dutch Natural History Survey. They found that the age at onset of ambulation is significantly delayed in boys with Duchenne. They suggest that age at onset of ambulation could be a primary outcome measure in clinical trials involving treatment in early infancy.

The objective of this study was to determine the effects of corticosteroids on major clinical outcomes of Duchenne in a large international cohort of patients. This study provides data on clinical outcomes across many healthcare settings and including a sizeable cohort of older patients. The data confirms the benefits of corticosteroid treatment on ambulation, need for scoliosis surgery, ventilation and, to a lesser extent, cardiomyopathy. This study underlines the importance of data collection via patient registries and the critical role of multi-center collaboration in the rare disease field.

This publication is an example of a study that recruited participants from DuchenneConnect rather than using registry data, and it is a study focused entirely on carrier women. Women were surveyed who have or had biological sons with Duchenne or Becker and were enrolled in DuchenneConnect. The objective was to identify barriers to carrier testing and the impact of carrier risk knowledge on cardiac and reproductive health management.

This article describes the frequency and type of genetic mutations reported in the TREAT-NMD Duchenne registries around the world, including DuchenneConnect. We request copies of each registrant’s genetic test report so we can share this data with the global registry and support research in Duchenne.

Dr. Stanley Nelson and his team at UCLA used data collected in DuchenneConnect between 2007 and 2011 for this study. They found that the data collected in DuchenneConnect is high quality and very similar to the data from natural history studies. This is important because using the Registry data for studies is much easier and less expensive than a traditional clinical trial. Dr. Nelson’s team also looked at corticosteroids as well as commonly used supplements to determine which ones, either alone or in combination, may help to prolong ambulation.

This publication is an example of a study that recruited participants from DuchenneConnect rather than using registry data. Funded by GlaxoSmithKline (GSK), this study revealed the different costs accompanying living with Duchenne and the overall financial burden carried by affected families. The research was carried out in collaboration with TREAT-NMD Duchenne registries in Germany, Italy, the United Kingdom and the United States (DuchenneConnect). Researchers asked patients and their primary caregivers to complete a questionnaire on their experience of living with Duchenne and the impact this had on medical care, employment, leisure time and quality of life. A total of 770 patients/caregivers completed the survey, with the US having the largest number of participants (284).

This article describes in detail how the TREAT-NMD national patient registries for Duchenne were established and how the registries have grown since their inception in 2007. The article highlights the registries success in fostering collaboration between academia, patient organizations and industry, ultimately leading to increased clinical trial opportunities for patients and translating directly to improvements in patient care and treatment options.

This is the first publication highlighting the registry data in DuchenneConnect. The data summarized was collected from the launch of DuchenneConnect in October 2007 through June 2011.